PROJECT SUMMARY Chronic subjective tinnitus is a common and sometimes disabling condition, with few effective treatments and no cure. Tinnitus is thought to involve dysfunction in central brain networks subsequent to peripheral injury or interference; thus, neurostimulation therapies that directly target central circuits are receiving growing interest. Of these, transcranial direct current stimulation (tDCS) is an attractive option, due to its relative affordability, mobility, and safety profile. A growing number of studies have demonstrated that tDCS of temporal/auditory cortex is effective at transiently reducing tinnitus symptoms, including tinnitus loudness and tinnitus distress. However, the results of previous clinical trials are variable, and a mechanistic understanding of tDCS and its therapeutic effects remains elusive. The main goal of this research is to lay the groundwork for improved, patient-centered approaches to noninvasive neurostimulation therapy for chronic tinnitus. Ultimately, we plan to use each patient?s unique brain-connectivity patterns to inform the placement of neurostimulation electrodes and improve therapeutic outcome. To accomplish this, we will first determine how the intrinsic activity and connectivity of auditory networks are affected during simultaneous tDCS-fMRI of auditory cortex, specifically targeting those patients who experience reduced tinnitus symptoms after tDCS (Aim 1). Then, we will perturb those networks with more focal stimulation using high-definition (HD) tDCS, using each patient?s unique functional neuroanatomy to position HD tDCS electrodes. Perturbation of target networks will be assessed with simultaneous HD tDCS-fMRI, and effects on clinical outcome will be measured (Aim 2). Though the primary goal of the proposed research is to optimize tDCS for the treatment of tinnitus, these studies will also provide a wealth of information regarding tinnitus pathophysiology and the mechanisms of tDCS more generally, which is being investigated for the treatment of a wide variety of brain disorders and injuries.